65996-50-1

Basic information

• Product Name: 1,5-Dihydropyrrolo[3,2-a]pyrimidine-2,4-dion
• Synonyms: 1,5-DIHYDRO-PYRROLO[3,2-A]PYRIMIDINE-2,4-DIONE;1,5-DIHYDRO-PYRROLO[3,2-D]PYRIMIDINE-2,4-DIONE;1,5-dihydro-pyrrolo[3,2-a]pyri;1,5-DIHYDROPYRROLO[3,2-A]PYRIMIDINE-2,4-DION;1-Pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione;1H,2H,3H,4H,5H-pyrrolo[3,2-d]pyriMidine-2,4-dione;5H-Pyrrolo[3,2-d]pyriMidine-2,4-diol
• CAS NO: 65996-50-1
• Molecular Formula: C₆H₅N₃O₂
• Molecular Weight: 151.12
• Product Categories: Ketone;Bases & Related Reagents;Intermediates;Nucleotides;pyrimidine;Heterocycle-Pyrimidine series
• Mol File: 65996-50-1.mol

Chemical Properties

• Melting Point: >360 °C(Solv: water (7732-18-5))
• Boiling Point: 607.6 °C at 760 mmHg
• Flash Point: 321.2 °C
• Appearance: /
• Density: 1.516 g/cm³
• Vapor Pressure: 2.35E-15mmHg at 25°C
• Refractive Index: 1.624
• Storage Temp.: 2-8°C
• PKA: 11.32±0.20(Predicted)
• CAS DataBase Reference: 1,5-Dihydropyrrolo[3,2-a]pyrimidine-2,4-dion(CAS DataBase Reference)
• NIST Chemistry Reference: 1,5-Dihydropyrrolo[3,2-a]pyrimidine-2,4-dion(65996-50-1)
• EPA Substance Registry System: 1,5-Dihydropyrrolo[3,2-a]pyrimidine-2,4-dion(65996-50-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 65996-50-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1,5-Dihydropyrrolo[3,2-a]pyrimidine-2,4-dion is used as a chemical intermediate for the preparation of pyrazolopyrimidine derivatives or analogs thereof. These derivatives are known as CCR4 function modulators, which have potential applications in the development of therapeutic agents targeting inflammatory and immune-related disorders. The modulation of CCR4 function can help regulate the migration and activity of immune cells, offering a strategy for treating diseases where immune dysregulation plays a significant role.

InChI:InChI=1/C6H5N3O2/c10-5-4-3(1-2-7-4)8-6(11)9-5/h1-2,7H,(H2,8,9,10,11)

Upstream product

• 116705-41-0 5-Nitro-2,4-dioxo-6-(β-dimethylaminovinyl)-1,2,3,4-tetrahydropyrimidine 
• 1560-54-9 allyltriphenylphosphonium bromide 
• 16632-21-6 5-nitro-6-methyluracil 
• 939979-34-7 ethyl 3-ureido-1H-pyrrole-2-carboxylate 
• 116705-41-0 (E)-6-(2-(dimethylamino)vinyl)-5-nitropyrimidine-2,4(1H,3H)-dione 
• 626-48-2 6-Methyluracil 
• 116705-41-0 (E)-6-(2-(dimethylamino)vinyl)-5-nitropyrimidine-2,4-diol 
• 252932-49-3 3-amino-2-ethoxycarbonylpyrrole hydrochloride 

Downstream Products

• 142544-99-8 C₃₂H₂₅N₃O₉ 
• 63200-54-4 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine 
• 114684-99-0 2-Chloro-4-(β-hydroxyethylamino)pyrrolo<3,2-d>pyrimidine 
• 114684-95-6 2-Chloro-4-piperidin-1-yl-5H-pyrrolo[3,2-d]pyrimidine 
• 114685-00-6 (2-Chloro-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-(2-cyclohexyl-ethyl)-amine 
• 114684-97-8 4-(2-Chloro-5H-pyrrolo[3,2-d]pyrimidin-4-ylamino)-butyric acid 
• 114684-98-9 (2-Chloro-5H-pyrrolo[3,2-d]pyrimidin-4-yl)-(1-methyl-2-phenyl-ethyl)-amine 
• 114684-94-5 2-Chloro-4<β-(cyclohexen-1'-yl)ethylamino>pyrrolo<3,2-d>pyrimidine 
• 114684-96-7 2-Chloro-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidine 
• 114685-04-0 N²,N⁴-Diphenyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine 
• 114685-02-8 N²,N⁴-Bis-(4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine 
• 114685-01-7 2,4-Bis<(β-cyclohexen-1'-yl)ethylamino>pyrrolo<3,2-d>pyrimidine 
• 113544-42-6 4-benzyloxy-2-chloro-5-(2-deoxy-β-D-erythropentofuranosyl)-5H-pyrrolo<3,2-d>pyrimidine 
• 113575-07-8 2,4-dichloro-5-(2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythropentofuranosyl)-5H-pyrrolo<3,2-d>pyrimidine 

Relevant articles and documents

Thermodynamic analysis of mRNA cap binding by the human initiation factor eIF4E via free energy perturbations

Eukaryotic mRNAs are appended at the 5′ end, with the 7-methylguanosine cap linked by a 5′-5′-triphosphate bridge to the first transcribed nucleoside (m7GpppX). Initiation of cap-dependent translation of mRNA requires direct interaction between the cap st

Structural and Biological Investigations for a Series of N-5 Substituted Pyrrolo[3,2-d]pyrimidines as Potential Anti-Cancer Therapeutics

Pyrrolo[3,2-d]pyrimidines have been studied for many years as potential lead compounds for the development of antiproliferative agents. Much of the focus has been on modifications to the pyrimidine ring, with enzymatic recognition often modulated by C2 and C4 substituents. In contrast, this work focuses on the N5 of the pyrrole ring by means of a series of novel N5-substituted pyrrolo[3,2-d]pyrimidines. The compounds were screened against the NCI-60 Human Tumor Cell Line panel, and the results were analyzed using the COMPARE algorithm to elucidate potential mechanisms of action. COMPARE analysis returned strong correlation to known DNA alkylators and groove binders, corroborating the hypothesis that these pyrrolo[3,2-d]pyrimidines act as DNA or RNA alkylators. In addition, N5 substitution reduced the EC50 against CCRF-CEM leukemia cells by up to 7-fold, indicating that this position is of interest in the development of antiproliferative lead compounds based on the pyrrolo[3,2-d]pyrimidine scaffold.

Anticancer Properties of Halogenated Pyrrolo[3,2-d]pyrimidines with Decreased Toxicity via N5 Substitution

Halogenated pyrrolo[3,2-d]pyrimidine analogues have shown antiproliferative activity in recent studies, with cell accumulation occurring in the G2/M stage without apoptosis. However, the mechanism of action and pharmacokinetic (PK) profile of these compounds has yet to be determined. To investigate the PK profile of these compounds, a series of halogenated pyrrolo[3,2-d]pyrimidine compounds was synthesized and first tested for activity in various cancer cell lines followed by a mouse model. EC50 values ranged from 0.014 to 14.5 μm, and maximum tolerated doses (MTD) in mice were between 5 and 10 mg kg?1. This indicates a wide variance in activity and toxicity that necessitates further study. To decrease toxicity, a second series of compounds was synthesized with N5-alkyl substitutions in an effort to slow the rate of metabolism, which was thought to be leading to the toxicity. The N-substituted compounds demonstrated comparable cell line activity (EC50 values between 0.83–7.3 μm) with significantly decreased toxicity (MTD=40 mg kg?1). Finally, the PK profile of the active N5-substituted compound shows a plasma half-life of 32.7 minutes, and rapid conversion into the parent unsubstituted analogue. Together, these data indicate that halogenated pyrrolo[3,2-d]pyrimidines present a promising lead into potent antiproliferative agents with tunable activity and toxicity, and rapid metabolism.

Pyrrolopyrimidine ketone compound and preparation method and application thereof

The invention relates to a pyrrolopyrimidine ketone compound and a preparation method and application thereof, and belongs to the technical field of medicine. The pyrrolopyrimidine ketone compound having a structural feature of formula I, or a pharmaceutically acceptable salt thereof has a very good inhibition effect on DPP-IV, and almost no effect on activity of DPP-VIII and DPP-IX, can effectively control the blood glucose concentration of diabetic rats, and is safe and low in toxicity through the verification of pharmacological and toxicological tests. After being prepared into a medicine, the compound provided by the invention not only has an obvious efficacy but also has very small side effects, thus greatly improving the administration convenience and patient use compliance, therefore, the compound has obvious advantages compared with the same kind of medicine. The formula is shown in the specification.

INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE

Disclosed herein are inhibitors of IRAK protein kinase of formula (I). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE

Disclosed herein are inhibitors of IRAK protein kinase. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

THIENO- AND PYRROLOPYRIMIDINE ANALOGUES AS ANTICANCER AGENTS AND METHODS OF USE THEREOF

The present invention provides for the design and synthesis of halogenated thieno- and pyrrolopyrimidine compounds that exhibit cancer proliferation inhibitory activity and the use thereof for cancer treatment.

Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines

In vitro evaluation of the halogenated pyrrolo[3,2-d]pyrimidines identified antiproliferative activities in compounds 1 and 2 against four different cancer cell lines. Upon screening of a series of pyrrolo[3,2-d]pyrimidines, the 2,4-Cl compound 1 was foun

Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization

A novel dipeptidyl peptidase IV inhibitor hit (5, IC50 = 0.86 μM) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 18o (IC50 = 1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T1/2: 2 h vs 4.9 h).

Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization

We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.